Implantable heart treatment systems, devices, and methods

ABSTRACT

Treatment of cardiac tissue via an implantable heart treatment device is described. A device embodiment includes, but is not limited to, a substrate configured for implantation within a body; an electromagnetic signal generator coupled to the substrate and configured to generate one or more electric signals configured to stimulate one or more tissues of a heart within the body; and an energy-carrier molecule delivery device coupled to the substrate and configured to supply one or more non-oxygen cellular energy sources to one or more tissues of the heart within the body.

If an Application Data Sheet (ADS) has been filed on the filing date ofthis application, it is incorporated by reference herein. Anyapplications claimed on the ADS for priority under 35 U.S.C. §§119, 120,121, or 365(c), and any and all parent, grandparent, great-grandparent,etc. applications of such applications, are also incorporated byreference, including any priority claims made in those applications andany material incorporated by reference, to the extent such subjectmatter is not inconsistent herewith.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of the earliest availableeffective filing date(s) from the following listed application(s) (the“Priority Applications”), if any, listed below (e.g., claims earliestavailable priority dates for other than provisional patent applicationsor claims benefits under 35 USC §119(e) for provisional patentapplications, for any and all parent, grandparent, great-grandparent,etc. applications of the Priority Application(s)).

PRIORITY APPLICATIONS

None.

If the listings of applications provided above are inconsistent with thelistings provided via an ADS, it is the intent of the Applicant to claimpriority to each application that appears in the DomesticBenefit/National Stage Information section of the ADS and to eachapplication that appears in the Priority Applications section of thisapplication.

All subject matter of the Priority Applications and of any and allapplications related to the Priority Applications by priority claims(directly or indirectly), including any priority claims made and subjectmatter incorporated by reference therein as of the filing date of theinstant application, is incorporated herein by reference to the extentsuch subject matter is not inconsistent herewith.

SUMMARY

In an aspect, an implantable heart treatment device includes, but is notlimited to, a substrate configured for implantation within a body; anelectromagnetic signal generator coupled to the substrate and configuredto generate one or more electric signals configured to stimulate one ormore tissues of a heart within the body; and an oxygenator coupled tothe substrate and configured to supply one or more oxygenated moleculesto one or more tissues of the heart within the body, the oxygenatorincluding a blood inlet portion, a blood outlet portion, and an oxygenexchange portion positioned between the blood inlet portion and theblood outlet portion, the oxygen exchange portion including a highsurface area oxygen exchanger configured to transfer one or moreoxygenated molecules from the high surface area oxygen exchanger toblood passing from the blood inlet portion to the blood outlet portion.

In an aspect, an implantable heart treatment device includes, but is notlimited to, a substrate configured for implantation within a body; anelectromagnetic signal generator coupled to the substrate and configuredto generate one or more electric signals configured to stimulate one ormore tissues of a heart within the body; a metabolic molecule supplydevice coupled to the substrate and configured to supply one or moremetabolic molecules to one or more tissues of the heart within the body;and control circuitry operably coupled to the electromagnetic signalgenerator and the metabolic molecule supply device, the controlcircuitry configured to generate one or more control signals accordingto at least a first control protocol and a second control protocol, thecontrol circuitry configured to generate one or more control signalsthat cause the electromagnetic signal generator to generate the one ormore electric signals upon execution of the first control protocol, thecontrol circuitry configured to generate one or more control signalsthat cause the electromagnetic signal generator to generate the one ormore electric signals and to generate one or more control signals thatcause the metabolic molecule supply device to supply the one or moremetabolic molecules upon execution of the second control protocol.

In an aspect, an implantable heart treatment device includes, but is notlimited to, a substrate configured for implantation within a body; anelectromagnetic signal generator coupled to the substrate and configuredto generate one or more electric signals configured to stimulate one ormore tissues of a heart within the body; and an energy-carrier moleculedelivery portion configured to supply one or more non-oxygen cellularenergy sources to one or more tissues of the heart within the body.

The foregoing summary is illustrative only and is not intended to be inany way limiting. In addition to the illustrative aspects, embodiments,and features described above, further aspects, embodiments, and featureswill become apparent by reference to the drawings and the followingdetailed description.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a schematic of an implantable heart treatment device inaccordance with one or more embodiments.

FIG. 2 is a schematic of an embodiment of a device such as shown in FIG.

FIG. 3A is a schematic of an embodiment of a device such as shown inFIG. 1.

FIG. 3B is a schematic of an embodiment of a device such as shown inFIG. 1.

FIG. 4A is a schematic of an embodiment of a device such as shown inFIG. 1.

FIG. 4B is a schematic of an embodiment of a device such as shown inFIG. 1.

FIG. 5A is a schematic of an embodiment of a device such as shown inFIG. 1.

FIG. 5B is a schematic of an embodiment of a device such as shown inFIG. 1.

FIG. 6 is a schematic of an embodiment of a device such as shown in FIG.

FIG. 7 is a schematic of an implantable heart treatment device inaccordance with one or more embodiments.

FIG. 8 is a schematic of an embodiment of a device such as shown in FIG.7.

FIG. 9 is a schematic of an embodiment of a device such as shown in FIG.7.

FIG. 10 is a schematic of an embodiment of a device such as shown inFIG. 7.

FIG. 11A is a schematic of an implantable heart treatment device inaccordance with one or more embodiments.

FIG. 11B is a schematic of an implantable heart treatment device inaccordance with one or more embodiments.

FIG. 12 is a schematic of an embodiment of a device such as shown inFIGS. 11A and 11B.

FIG. 13 is a schematic of an embodiment of a device such as shown inFIGS. 11A and 11B.

FIG. 14 is a flowchart of a method of treating a heart with an implantedheart treatment device.

FIG. 15 is a flowchart of a method of treating a heart with an implantedheart treatment device.

FIG. 16 is a flowchart of a method of treating a heart with an implantedheart treatment device.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings, which form a part hereof. In the drawings,similar symbols typically identify similar components, unless contextdictates otherwise. The illustrative embodiments described in thedetailed description, drawings, and claims are not meant to be limiting.Other embodiments may be utilized, and other changes may be made,without departing from the spirit or scope of the subject matterpresented here. As used herein, the words “configured” and “adapted” areinterchangeable unless the context dictates otherwise.

Systems and devices are described for treating cardiac tissue via animplantable heart treatment device that utilizes one or more mechanismsfor therapy, including, but not limited to, electric stimulation,oxygenation, energy transport, and chemical species delivery.Cardiovascular disease remains the leading cause of deaths globally,with approximately 300,000 Americans dying annually from “sudden cardiacdeath,” primarily from severe and prolonged ventricular fibrillation. Onaverage, a human ventricular-fibrillating heart exhausts its entiremyoglobin-based oxygen reserve in a fifty to seventy-five secondtime-frame after the blood pressure drops at the top of the coronaryartery tree. Afterwards, the cardiac tissue is so “stunned” thatattempts to re-start or resynchronize via electric defibrillator arestatistically likely to fail. The myocardium is unable to functionfollowing the fifty to seventy-five second time-frame unless thecondition is remediated. However, clinical records indicate thatexternal cardiopulmonary resuscitation is typically insufficient forsuch remediation, which often results in death of a patient. In anembodiment, the systems and devices described herein may be used totreat cardiac tissue during or following a fibrillation event withelectric stimulation and one or more of oxygenation, energy transport,and chemical species delivery.

In embodiments, the systems and devices described herein employ asubstrate configured for implantation within a body, such as proximatecardiac tissue of the heart. The substrate can support, or have coupledthereto, an electromagnetic signal generator and one or more of anoxygenator, a metabolic molecule supply device, and an energy-carriermolecule delivery portion. In embodiments, an implantable hearttreatment device includes control circuitry employing at least twocontrol protocols for action to the cardiac tissue, with a first controlprotocol causing activation of an electromagnetic signal generator, andwith a second control protocol causing activation of an electromagneticsignal generator and a metabolic molecule supply device.

As used herein, a “fibrillation event” includes a ventricularfibrillation event. Ventricular fibrillation is a cause of cardiacarrest and sudden cardiac death. The ventricular muscle fibers contractrandomly causing a complete failure of ventricular function. Most casesof ventricular fibrillation occur in patients with pre-existing knownheart disease but the precise nature of the underlying cause ofventricular fibrillation is not currently known. In an embodiment, shownin FIG. 1, a system (or device) 100 is configured to treat cardiactissue, such as cardiac tissue during and following a fibrillationevent. The system 100 includes, but is not limited to, a substrate 102,an electromagnetic signal generator 104, and an oxygenator 106. Inembodiments, the substrate 102 is configured for implantation within abody of an individual and to house or support other portions of thesystem 100. The structure of the substrate 102 can conform to a surfaceof a body portion next to which or within which the system 100 isconfigured to reside. In embodiments, portions of the system 100 and thesubstrate 102 which are exposed to the individual's body comprise one ormore biocompatible materials, for example, stainless steel, titanium,nitinol, gold, biocompatible ceramics, stainless steel, shape memorymaterial, biocompatible polymer, polyester, polyamide,polytetrafluoroethylene, polyalkenes, polyethylene, ultra-high molecularweight polyethylene, copolymers or composites thereof, and the like. Inembodiments, at least a portion of the substrate 102 is configured as ahousing hermetically sealed from the external environment (e.g., theinterior of the individual's body).

The electromagnetic signal generator 104 is coupled to the substrate 102and is configured to generate one or more time varying electric signalsconfigured to stimulate one or more tissues of the heart within theindividual's body. In embodiments, the electromagnetic signal generator104 includes one or more of a pacemaker device, a defibrillator device(e.g., an implantable cardioverter-defibrillator), an anti-tachycardiadevice, or other device configured to affect one or more physiologicalproperties of the heart via electric signals. In embodiments, theelectromagnetic signal generator 104 is configured to generate one ormore time varying electric signals for the electric treatment of cardiacsymptoms resulting from cardiac disease or disorder, including but notlimited to myocarditis, cardiomyopathy, cardiogenic shock, congenitaldefect, cardiac arrest, and the like. In embodiments, theelectromagnetic signal generator 104 includes an electrode configured tocontract the cardiac tissues upon application of one or more electricsignals. For instance, the electrode can be positioned on an exteriorsurface of the substrate 102, configured for contact with one or morecardiac tissues. In embodiments, the electrode includes one or moreelectrode leads projecting from the electromagnetic signal generator 104or the substrate 102 to affect cardiac tissue located remotely from theelectromagnetic signal generator 104 or the substrate 102. Inembodiments, the electromagnetic signal generator 104 is powered by apower source including at least one of a battery, a capacitor, athermoelectric generator, a piezoelectric generator, amicroelectromechanical systems (MEMS) generator, and abiomechanical-energy harvesting generator. In an embodiment, thebiomechanical-energy harvesting generator is configured to generatepower based on a blood flow of the individual in which the system 100 isimplanted.

The oxygenator 106 is coupled to the substrate 102 and is configured tosupply one or more oxygenated molecules to one or more tissues of theheart of the individual in which the system 100 is implanted. Inembodiments, the oxygenator 106 is a blood-gas exchanger having anexchange membrane configured to regulate an exchange of oxygenatedmolecules between the oxygenator 106 and a flow of blood through theoxygenator 106. For example, in an embodiment, shown in FIG. 2, theoxygenator 106 includes a blood inlet portion 200, an oxygen exchangeportion 202, and a blood outlet portion 204. The blood inlet portion 200is configured to receive blood from the individual in which the system100 is implanted into the oxygenator 106 to provide the blood-gasexchange interface. The blood outlet portion 204 is configured to returnoxygenated blood to the individual following the blood-gas exchange inthe oxygen exchange portion 202, such as by delivery to a vein, deliveryto an artery, delivery directly within the heart, and the like. Theblood inlet portion 200 and the blood outlet portion 204 can includevarious fluid-flow passageways and ports suitable for the transport ofblood, and can include, but are not limited to, biocompatible capillaryconduits/tubes and micron-scale conduits/tubes (e.g., sufficient totransport at least one red blood cell through the interior of the tube).

In embodiments, the conduits of the system 100 have a minimum internaldiameter of greater than 10 microns to accommodate the passage of redblood cells. For example, in embodiments, at least a portion of theconduits of the system 100 have a minimum internal diameter of between10 microns and 12 microns to accommodate the passage of red blood cellsthrough the system 100. The internal diameter can be larger or smallerthan this range, due to manufacturing tolerances, design specificationsdependent on types of red blood cells, and so forth, to accommodate thepassage of red bloods cells, such as in a flow of singular red bloodscells.

The source of the blood to be received by the blood inlet portion 200and the destination of the oxygenated blood to be returned by the bloodoutlet portion 204 can depend on design characteristics of the system100, including size of the substrate 102, number of inlets of the bloodinlet portion 200, number of outlets of the blood outlet portion 204,portion of cardiac tissue to be treated, presence or absence of a bloodpump, and so forth. The source of the blood to be received by the bloodinlet portion 200 and the destination of the oxygenated blood to bereturned by the blood outlet portion 204 can include sources anddestinations employed for extracorporeal membrane oxygenators (see,e.g., Hung, Vuylsteke, and Valchanov, Extracorporeal MembraneOxygenation: Coming to an ICU Near You, J. Intensive Care Society., Vol.13, 31-38 (2012), which is incorporated herein by reference).

For example, in an embodiment, the blood inlet portion 200 includes oneor more ports configured to receive blood from one or more cardiacveins, such as from one or more of the great cardiac vein (e.g., leftcoronary vein), the middle cardiac vein, the small cardiac vein, and atleast one of the anterior cardiac veins (e.g., anterior veins of rightventricle); the blood is then oxygenated by the oxygen exchange portion202 (described herein below), and subsequently returned by the bloodoutlet portion 204 having at least one port positioned within at leastone coronary artery, such as within a portion of one or more of the leftcoronary artery, the right coronary artery, and one or moresubendocardial artery.

In an embodiment, the blood inlet portion 200 includes one or more portsin contact with blood from an internal jugular vein, and configured toreceive blood from one or more of the superior vena cava (SVC) and theinferior vena cava (IVC), where after oxygenation of the blood occurs inthe oxygen exchange portion 202, the oxygenated blood is returned to theindividual via a port of the blood outlet portion 204 positioned withinat least one coronary artery, such as within a portion of one or more ofthe left coronary artery, the right coronary artery, and one or moresubendocardial artery. The blood inlet portion 200 can include at leasttwo ports, with at least one port positioned to receive blood from thesuperior vena cava (SVC) and at least one port positioned to receiveblood from the inferior vena cava (IVC).

In an embodiment, the blood inlet portion 200 includes one or more portsin contact with blood from an internal jugular vein, and configured toreceive blood from one or more of the superior vena cava (SVC) and theinferior vena cava (IVC), where after oxygenation of the blood occurs inthe oxygen exchange portion 202, the oxygenated blood is returned to theindividual via a port of the blood outlet portion 204 positioned withinor proximate to the right atrium of the heart. The blood inlet portion200 can include at least two ports, with at least one port positioned toreceive blood from the superior vena cava (SVC) and at least one portpositioned to receive blood from the inferior vena cava (IVC).

In an embodiment, the blood inlet portion 200 includes a port in contactwith blood from an internal jugular vein, and is configured to receiveblood from one or more of the superior vena cava (SVC) and the inferiorvena cava (IVC), where after oxygenation of the blood occurs in theoxygen exchange portion 202, the oxygenated blood is returned to theindividual via a port of the blood outlet portion 204 positioned withinor proximate to one or more of the ascending aorta, the descendingaorta, and the aortic arch.

In an embodiment, the blood inlet portion 200 includes a port in contactwith blood from at least one of the pulmonary artery and the rightventricle, where after oxygenation of the blood occurs in the oxygenexchange portion 202, the oxygenated blood is returned to the individualvia a port of the blood outlet portion 204 positioned within orproximate to one or more of the pulmonary vein, and the left atrium. Inan embodiment, the blood inlet portion 200 includes a port in contactwith blood from at least one of the ascending aorta, the descendingaorta, the aortic arch, and the left ventricle, where after oxygenationof the blood occurs in the oxygen exchange portion 202, the oxygenatedblood is returned to the individual via a port of the blood outletportion 204 positioned within or proximate to one or more of thesuperior vena cava, the inferior vena cava, and the right atrium. In anembodiment, the blood inlet portion 200 includes a port in contact withblood from at least one of the ascending aorta, the descending aorta,the aortic arch, and the left ventricle, where after oxygenation of theblood occurs in the oxygen exchange portion 202, the oxygenated blood isreturned to the individual via a port of the blood outlet portion 204positioned within or proximate to one or more of the pulmonary vein, andthe left atrium. In an embodiment, the blood inlet portion 200 includesa port in contact with blood from at least one of the descending aorta,the mesenteric artery, the iliac artery, and the femoral artery, whereafter oxygenation of the blood occurs in the oxygen exchange portion202, the oxygenated blood is returned to the individual via a port ofthe blood outlet portion 204 positioned within or proximate to one ormore of the femoral vein, the iliac vein, the abdominal vena cava, theinferior vena cava, and the right atrium. Other configurations arepossible and are not limited to the above-provided configurations.

In some embodiments, the oxygenator 106 includes a blood pump 208. Theblood pump 208 may be coupled to the blood inlet portion 200, and may beused to force blood through the oxygen exchange portion 202 (e.g.,overcoming the flow resistance through high surface area oxygenexchanger 206, described further herein). In some embodiments, the bloodpump 208 may be controlled so as to match the pressure at the bloodoutlet portion 204 to that of the blood in the destination lumen. Bloodpump 208 may include the same type of blood pumps (e.g., centrifugaltypes, or roller types) typically used in conjunction withextracorporeal membrane oxygenators. Unlike pumps used in implantable“artificial hearts,” the blood pump 208 can be configured to operateonly for short durations, i.e., during a fibrillation event. The bloodpump 208 may facilitate operation of embodiments where the blood inletportion 200 is coupled to a vein or a heart atrium, and may be optionalin some embodiments (e.g., embodiments where the blood inlet portion 200is coupled to an artery or heart ventricle).

In some embodiments, the oxygenator 106 includes a controllable valve210. The valve 210 may be coupled to the blood inlet portion 200, andmay be closed during normal situations to prevent blood flow through theoxygenator (e.g., through oxygen exchange portion 202), and opened onlyduring fibrillation events.

The oxygen exchange portion 202 of the oxygenator 106 includes ablood-gas interface for blood-gas exchange to oxygenate the bloodreceived by the blood inlet portion 200. As shown in FIG. 2, the oxygenexchange portion 202 includes a high surface area oxygen exchanger 206as a blood-gas interface to transfer one or more oxygenated moleculesfrom the high surface area oxygen exchanger 206 to blood passing fromthe blood inlet portion 200 to the blood outlet portion 204. As usedherein, the term “high surface area” is used with a context of a surfacearea configured for the exchange of materials, where the surface area isbetween approximately 0.001 square meters (m²) and approximately 5square meters (m²), where the surface area can vary depending onmanufacturing tolerances, material specifications, and so forth (see,e.g., Gaylor, Membrane oxygenators: current developments in design andapplication, J. Biomed. Eng., Vol. 10, 541-547 (1988), which isincorporated herein by reference). In general, the high surface areaoxygen exchanger 206 facilitates gas exchange between the blood and gasphases by providing a significant surface area for oxygen diffusion intoand through the blood phase, resulting in an oxygenated blood stream. Inembodiments, the high surface area oxygen exchanger 206 includes amembrane-based oxygenator, where the membrane is an oxygen-permeablemembrane that is permeable to the oxygenated molecules, but not to theblood. The oxygen can permeate through the membrane based onconcentration gradients, where the blood can include a lower oxygenconcentration, thereby facilitating diffusion of the oxygenatedmolecules through the membrane and into the blood.

In embodiments, the membrane includes a plurality of hollow fibersthrough which blood or oxygenated molecules are passed, where thematerial that is not included in the hollow fibers (i.e., thecorresponding oxygenated molecules or blood) is passed along theexterior of the hollow fibers. The number of hollow fibers utilizedgenerally depends on the desired surface area of the high surface areaoxygen exchanger 206, the size of the hollow fibers, the material of thehollow fibers, and so forth. In embodiments, the high surface areaoxygen exchanger 206 includes between approximately one thousand and tenmillion hollow fibers. In embodiments, the hollow fibers are constructedfrom biocompatible materials, including but not limited to, silicone,polypropylene, and polymethylpentene (e.g., 4-methyl-1-pentene, PMP),and can include one or more coatings thereon, including but not limitedto, heparin and silicone (see, e.g., Lim, The history of extracorporealoxygenators, Anaesthesia, Vol. 61, 984-995 (2006), which is incorporatedherein by reference). In embodiments, the hollow fibers are constructedfrom polypropylene, which can include micropores in the polypropylenestructure. The micropores are configured to permit the diffusion of gasthrough the pores to oxygenate the blood that flows through the fibers,or that is flowing on an exterior of the fiber (e.g., an inverse-flowconfiguration). In embodiments, the hollow fibers are constructed frompolymethylpentene (PMP), which is a gas permeable polymer material,through which the oxygenated material can pass to the blood located inthe interior or on the exterior of the hollow fibers.

Referring to FIG. 3A, the high surface area oxygen exchanger 206includes a plurality of hollow fibers 300 arranged in a shell and tubeconfiguration having oxygenated material (e.g., a flow of oxygenatedgas) through the interior 302 of the hollow fibers 300 (flow shown as304). Blood is passed over the exterior 306 of the hollow fibers 300(flow shown as 308). Alternatively, the blood can be passed through theinterior 302 of the hollow fibers 300, where the oxygenated materialwould then pass over the exterior 306 of the hollow fibers. Referring toFIG. 3B, the high surface area oxygen exchanger 206 includes a pluralityof hollow fibers 300 arranged in a cross-flow configuration, where afirst set of hollow fibers 300 a are arranged substantiallyperpendicularly to a second set of hollow fibers 300 b. Each of thefirst set of hollow fibers 300 a and the second set of hollow fibers 300b include a flow of oxygenated material through the interior of the 302of the hollow fibers 300 (flow shown as 304). Blood is passed over theexterior 306 of the hollow fibers 300 of the first set of hollow fibers300 a and the second set of hollow fibers 300 b (flow shown as 308). Thecross-flow configuration can facilitate mixing of the blood forefficient gas diffusion through the blood, to oxygenate the blood withthe oxygenated material transported through the micropore structure ofthe hollow fibers 300. Alternatively, the blood can be passed throughthe interior 302 of the hollow fibers 300, where the oxygenated materialwould then pass over the exterior 306 of the hollow fibers. While FIG.3B shows a cross-flow configuration having an approximately ninetydegree offset between the first set of hollow fibers 300 a and thesecond set of hollow fibers 300 b, other offsets can be utilized, suchas for example, an offset of between forty-five and ninety degrees. Inan embodiment, blood flow within the high surface area oxygen exchanger206 resembles an artery-capillary-vein geometry, involving passagethrough a low-pressure drop supply manifold coupled to the blood inletportion 200 (the “artery” analog), short flow passages through or aroundan array of hollow fibers 300 in the oxygen exchange portion 202 (the“capillary” analog), and then passage through a low-pressure drop returnmanifold coupled to the blood outlet portion 204 (the “vein” analog). Inan embodiment, use of 20 micron diameter hollow fibers in a 25%fill-factor array results in a volume for the oxygen exchange portion202 of 20 cm³ for a membrane surface area of 1 m². Utilization of anequal volume for the supply and return manifolds results in a 40 cm³volume for the high surface area oxygen exchanger 208.

In embodiments, the oxygenated molecules are stored in vivo in thesystem 100, generated in vivo by the system 100, or a combination ofstored in and generated by the system 100. For example, referring to theembodiment shown in FIG. 4A, the system includes a reservoir 400 influid communication with the oxygenator 106. The reservoir 400 isconfigured to store the oxygenated material within the reservoir and tosupply the oxygenated material to the oxygenator 106. The supply of theoxygenated material from the reservoir 400 to the oxygenator 106 can beregulated by control circuitry, such as for example, by regulating avalve or port between the reservoir 400 and the oxygenator 106.Alternatively or additionally, the system can include reservoir 400 as acomponent of the oxygenator 106, as shown in FIG. 4B. In embodiments,such as the embodiment shown in FIG. 5, the system 100 includes anoxygenated material generator 500 configured to generate the oxygenatedmaterial within the system 100, which can include one or more of achemical reactor 502 and an electrochemical reactor 504. The chemicalreactor 502 is configured to generate the oxygenated material as aproduct of a chemical reaction occurring within the system 100 (orwithin the oxygenator 106, as shown in FIG. 5B). For example, thechemical reaction can include, but is not limited to, an alkali metalcombustion with peroxide (e.g., lithium combustion with peroxide,degradation of hydrogen peroxide), absorption of carbon dioxide with analkali metal oxide (e.g., Li₂O₂), and so forth. For example, thechemical reaction can include a reaction of sodium chlorate, bariumperoxide, and potassium chlorate (as used in some chemical oxygengenerators for aircraft, available for example from Molecular ProductsAmerica). For example, the chemical reactor 502 can include an oxygencandle (i.e., a chlorate candle). A discussion of oxygen candles ispresented in “Lithium Perchlorate Oxygen Candle. Pyrochemical Source ofPure Oxygen”, by M. M. Markowitz, D. A. Boryta, Harvey Stewart Jr., Ind.Eng. Chem. Prod. Res. Dev., 1964, 3 (4), pp 321-330 (which isincorporated herein by reference). In embodiments, the chemical reactor502 includes thermal insulation to limit exposure of body tissue tothermal energy associated with chemical oxygen generation. Inembodiments, the chemical reactor 502 includes a catalyst configured tofacilitate the chemical reaction. The electrochemical reactor 504 isconfigured to generate the oxygenated material as a product of anelectrochemical reaction occurring within the system 100 (or within theoxygenator 106, as shown in FIG. 5B). For example, the electrochemicalreaction can include, but is not limited to, electrolysis of water togenerate gaseous oxygen. The electrochemical reaction can include otheroxygen-generating electrochemical reactions including, but not limitedto, Ag₂O with I₂, Na₂O with I₂, Ag₂O with S, and other electrochemicalreactions disclosed in U.S. Pat. No. 7,122,027 (which is incorporatedherein by reference). In embodiments, the oxygenated material isgenerated on demand, such as regulated by control circuitry, forimmediate use by the oxygenator, or can be generated in advance ofrequiring its use, where the oxygenated material is stored until needed.In embodiments, the oxygenated material is adsorbed to a surface of thehigh surface area oxygen exchanger 206, such as, for example, theinterior 302 or exterior 306 of the hollow fibers 300.

In embodiments, the oxygenated molecules that are transferred betweenthe oxygenator 106 and the blood include one or more carrier moleculesconfigured to transport gaseous oxygen (e.g., O₂). A carrier moleculecan include an individual molecule (e.g., a perflurocarbon) or caninclude a multi-molecular structure (e.g., a liposome or micelle). Forexample, the carrier molecules utilized by the oxygenator 106 caninclude, but are not limited to, liposomes, micelles, andperflurocarbons. In embodiments, the oxygenated molecules within theassociated carrier molecules are stored in the reservoir 400, for use bythe oxygenator 106 to transfer one or more of the oxygen stored thereinand carrier molecule with the oxygenated molecule.

In embodiments, the system 100 is configured to activate one or more ofthe electromagnetic signal generator 104 and the oxygenator 106 asdirected by control signals from control circuitry. For example, in anembodiment, shown in FIG. 6, the system 100 includes control circuitry600 configured to provide one or more control signals to theelectromagnetic signal generator 104 and the oxygenator 106 foractivation of the respective devices. In embodiments, the controlcircuitry 600 generates the control signals based on measurements fromone or more physiological parameter sensors (also called “physiologicalsensors” herein). The physiological parameter sensors can be resident,i.e., included as a component of the system 100 (e.g., shown asphysiological sensor 602 in FIG. 6), located remotely from the system100, or a combination of resident and remote sensors, and such sensorscan measure a physiological parameter representative of a condition ofthe heart. In embodiments, the physiological sensor includes a bloodpressure sensor configured to measure a sudden blood pressure drop of anaortic region, a coronary artery, a cardiac vein, and the like todetermine whether the heart is undergoing a fibrillation event. Forexample, the physiological sensor can measure the blood pressure at theaortic arch to determine whether the heart is undergoing a fibrillationevent. In embodiments, the physiological sensor includes an oxygenationsensor configured to measure a cardiac oxygenation level, such as anoxygenation level of cardiac tissue-based myoglobin. In embodiments, thephysiological sensor includes one or more electrodes configured tomeasure a heart electrical activity level, such as the temporal andspatial progression of a heart's depolarization wave; for example an ECGor EKG. When a fibrillation event is detected by the physiologicalsensor, the physiological sensor (or associated control circuitry) canprovide an indication (e.g., in the form of sense signals, controlsignals, and so forth) to the control circuitry 600 regarding thefibrillation event. This indication can include, but is not limited to,whether a fibrillation event is occurring, the current duration of thefibrillation event, and the like. In embodiments, an ECG is performed byutilizing sense signals from the physiological sensors to determinewhether a heart is undergoing ventricular fibrillation. Suchdeterminations can be based on detection algorithms that differentiatebetween various cardiac states indicative of cardiac arrest, such asventricular fibrillation, and cardiac states that may not be indicativeof cardiac arrest or that do not require electric stimulation ortreatment, such as a fast but stable sinus rhythm, a heart that recentlyunderwent successful defibrillation, and so forth. The detectionalgorithms can include, but are not limited to, a threshold crossinginterval (TCI) algorithm, an autocorrelation (ACF) algorithm, aventricular fibrillation filter (VF filter) algorithm, a spectralalgorithm, a complexity measure algorithm, a standard exponential (STE)algorithm, a modified exponential algorithm (MEA), a signal comparisonalgorithm (SCA), a wavelet based algorithm, a Li algorithm, and aTompkins algorithm (see, e.g., Amann et al., Reliability of old and newventricular fibrillation detection algorithms for automated externaldefibrillators, BioMedical Engineering Online, 4:60 (2005),doi:10.1186/1475-925X-4-60, which is incorporated herein by reference).The control circuitry 600 can then provide control signals to one ormore of the electromagnetic signal generator 104 and the oxygenator 106for treatment of the cardiac tissue during the fibrillation event. Inembodiments, the control circuitry 600 is configured to make adetermination regarding whether a fibrillation event is occurring, acurrent duration of a fibrillation event, and the like based on one ormore sense signals received from the physiological sensors. Inembodiments, the control circuitry 600 provides control signals to theelectromagnetic signal generator 104, independent of the oxygenator 106.In embodiments, the control circuitry 600 provides control signals toeach of the electromagnetic signal generator 104 and the oxygenator 106.

In embodiments, the control circuitry 600 generates the control signalsbased on commands issued by an external control device (shown as 604 inFIG. 6). In embodiments, the control circuitry 600 is a residentcomponent that is coupled to the substrate 102. In embodiments, thecontrol circuitry 600 can send and receive signals between externalcontrol device 604 via associated wireless communication methodsincluding, but not limited to acoustic communication signals, opticalcommunication signals, radio communication signals, infraredcommunication signals, ultrasonic communication signals, and the like.The control circuitry 600 can include a microprocessor, a centralprocessing unit (CPU), a digital signal processor (DSP), anapplication-specific integrated circuit (ASIC), a field programmablegate entry (FPGA), or the like, or any combinations thereof, and caninclude discrete digital or analog circuit elements or electronics, orcombinations thereof. In one embodiment, the computing device includesone or more ASICs having a plurality of predefined logic components. Inone embodiment, the computing device includes one or more FPGAs having aplurality of programmable logic commands.

In embodiments, the oxygenator 106 is configured to supply one or morematerials to the blood in addition to the oxygenated molecules. Forexample, the materials in addition to the oxygenated molecules caninclude, but are not limited to, hydrogen sulfide (H₂S), carbon dioxide(CO₂), carbon monoxide (CO), nitric oxide (NO), nitrous oxide (N₂O),nitrogen dioxide (NO₂), and iodide (e.g., iodide ions (I⁻) and saltsthereof (e.g., sodium iodide (Na)), see, e.g., Iwata et al., IodideProtects Heart Tissue from Reperfusion Injury, PLOS ONE, Vol. 9, 11,e112458 (2014), which is incorporated herein by reference). Thesematerials can be used to protect the cardiac tissue from injury (e.g.,ischemia reperfusion injury) during and after a fibrillation event, tocontrol metabolic processes of cardiac tissue during and after afibrillation event, to provide localized or systemic anesthetic, and soforth.

In an embodiment, shown in FIG. 7, a system (or device) 700 isconfigured to treat cardiac tissue, such as cardiac tissue during andfollowing a fibrillation event. The system 700 includes, but is notlimited to, a substrate 702, an electromagnetic signal generator 704, ametabolic molecule supply device 706, and control circuitry 708configured to execute a first control protocol 710 and a second controlprotocol 712. While two control protocols are shown, the controlcircuitry 708 is not limited to two control protocols, and can executemore than two, as desired. The substrate 702 is configured forimplantation within a body of an individual and to house or supportother portions of the system 700. In embodiments, the structure of thesubstrate 702 is similar to, or the same as, the structure of thesubstrate 102 described herein, with corresponding functionalities. Theelectromagnetic signal generator 704 is coupled to the substrate 702 andis configured to generate one or more electric signals configured tostimulate one or more tissues of the heart within the individual's body.In embodiments, the structure of the electromagnetic signal generator704 is similar to, or the same as, the structure of the electromagneticsignal generator 104 described herein, with correspondingfunctionalities.

The metabolic molecule supply device 706 is coupled to the substrate 702and is configured to supply one or more metabolic molecules to one ormore tissues of the heart within the body. The term “metabolic molecule”is used with a context for describing molecules utilized by a biological(e.g., human) body for metabolic processes, or those materials thataffect the metabolic process of the body, and can include, but are notlimited to, oxygenated molecules and iodide. In embodiments, themetabolic molecules are stored by the system 700 in vivo, such as in areservoir of the system 700. In embodiments, the metabolic moleculesupply device 706 includes an oxygenator, such as oxygenator 106described herein for the transfer of oxygenated molecules between theoxygen exchange portion 202 and blood passing from the blood inletportion 200 to the blood outlet portion 206. In embodiments, themetabolic molecule supply device 706 includes a reservoir (e.g.,reservoir 714) or is in fluid communication with a reservoir, or acombination of both, where the reservoir is configured to store themetabolic molecules for use by the metabolic molecule supply device 706to supply the one or more metabolic molecules to the cardiac tissue.

The control circuitry 708 is configured to generate one or more controlsignals based on execution of the first control protocol 710 and thesecond control protocol 712. In embodiments, upon execution by thecontrol circuitry 708 of the first control protocol 710, the controlcircuitry 708 generates one or more control signals that cause theelectromagnetic signal generator 704 to generate one or more electricsignals configured to stimulate cardiac tissues. For example, the firstcontrol protocol 710 includes instructions that can dictate actions forthe system 700 to take during a fibrillation event, but prior tosubstantial exhaustion (e.g., more than 25%, more than 50%, more than75%, more than 90%) of myoglobin-based oxygen storage of the heart. Inembodiments, upon execution by the control circuitry 708 of the secondcontrol protocol 712, the control circuitry 708 generates one or morecontrol signals that cause the electromagnetic signal generator 704 togenerate one or more electric signals configured to stimulate cardiactissues and the control circuitry 708 generates one or more controlsignals that cause the metabolic molecule supply device 706 to supplythe one or more metabolic molecules to one or more cardiac tissues. Forexample, the second control protocol 712 can provide direction regardingactions for the system 700 to take during an extended fibrillation eventwhere metabolic molecules, such as oxygen are beneficial in attemptingto treat a heart undergoing systemic shock associated with exhaustion ofmyoglobin-based oxygen storage (e.g., a period of about fifty seconds toabout seventy-five seconds following onset of a fibrillation event). Inembodiments, the control circuitry 708 determines which control protocolto execute based on measurements from one or more physiological sensors.The one or more physiological sensors can be included as a component ofthe system 700 (e.g., shown as physiological sensor 716 in FIG. 7),located remotely from the system 700, or a combination of resident andremote sensors. In embodiments, the physiological sensor is a bloodpressure sensor configured to measure a blood pressure of an aorticregion, a coronary artery, a cardiac vein, and the like, to determinewhether the heart is undergoing a fibrillation event. For example, thephysiological sensor can measure the blood pressure at the aortic archto determine whether the heart is undergoing a fibrillation event. Inembodiments, the physiological sensor includes an oxygenation sensorconfigured to measure a cardiac oxygenation level, such as anoxygenation level of cardiac tissue-based myoglobin. In embodiments, thephysiological sensor includes one or more electrodes configured tomeasure a heart electrical activity level. When a fibrillation event isdetected by the physiological sensor, the physiological sensor (orassociated control circuitry) can provide an indication (e.g., in theform of sense signals, control signals, and so forth) to the controlcircuitry 708 regarding the fibrillation event. This indication caninclude, but is not limited to, whether a fibrillation event isoccurring, the current duration of the fibrillation event, and the like.The control circuitry 708 can then provide control signals to at leastone of execute the first control protocol, execute the second controlprotocol, cease execution of the first control protocol, and ceaseexecution of the second control protocol. The control circuitry 708 canthen provide control signals to one or more of the electromagneticsignal generator 704 and the metabolic molecule supply device 706 fortreatment of the cardiac tissue during the fibrillation event. Inembodiments, the control circuitry 708 provides control signals to theelectromagnetic signal generator 704, independent of the metabolicmolecule supply device 706, such as provided by the first controlprotocol 710. In embodiments, the control circuitry 708 provides controlsignals to each of the electromagnetic signal generator 104 and themetabolic molecule supply device 706, such as provided by the secondcontrol protocol 712.

In embodiments, the control circuitry 708 generates the control signalsbased on commands issued by an external control device (shown as 800 inFIG. 8). In embodiments, the control circuitry 708 can send and receivesignals between external control device 800 via associated wirelesscommunication methods including, but not limited to acousticcommunication signals, optical communication signals, radiocommunication signals, infrared communication signals, ultrasoniccommunication signals, and the like. The control circuitry 708 caninclude a microprocessor, a central processing unit (CPU), a digitalsignal processor (DSP), an application-specific integrated circuit(ASIC), a field programmable gate entry (FPGA), or the like, or anycombinations thereof, and can include discrete digital or analog circuitelements or electronics, or combinations thereof. In one embodiment, thecomputing device includes one or more ASICs having a plurality ofpredefined logic components. In one embodiment, the computing deviceincludes one or more FPGAs having a plurality of programmable logiccommands. In embodiments, the control circuitry 708 can wirelesslytransmit the control signals or information associated with the controlsignals to an external device, e.g., to report control circuitryactions.

In embodiments, the control circuitry 708 is configured to receive oneor more control signals from the external control device 800 and to makea determination regarding a defibrillation state. For example, thecontrol circuitry 708 can receive one or more control signals from theexternal control device 800, whereby the control circuitry 708 directsone or more physiological sensors to measure a physiological parameterassociated with cardiac activity (e.g., blood pressure, bloodoxygenation level, myoglobin oxygenation level, and the like, which canbe representative of a condition of the heart) to determine adefibrillation state of the individual in which the system 700 isimplanted. Based upon the physiological parameter of the heart, thecontrol circuitry 708 can execute the first control protocol 710 or thesecond control protocol 712. For example, in embodiments, when thephysiological parameter of the heart indicates a fibrillation event isoccurring, and the myoglobin-based oxygen is not exhausted (e.g., aperiod between onset of a fibrillation event and between approximatelyfifty seconds and seventy-five seconds following the onset of thefibrillation event), the control circuitry 708 executes the firstcontrol protocol 710, resulting in activation of the electromagneticsignal generator 704 for electric stimulation of the cardiac tissue. Inembodiments, when the physiological parameter of the heart indicates afibrillation event is occurring, and the myoglobin-based oxygen issubstantially exhausted (e.g., a period of fifty seconds to seventy-fiveseconds following onset of a fibrillation event), the control circuitry708 executes the second control protocol 712, resulting in activation ofeach of the electromagnetic signal generator 704 and the metabolicmolecule supply device 706 for treatment of the cardiac tissue, such asthrough electric stimulation of the cardiac tissue and delivery ofoxygenated molecules to the cardiac tissue. In some embodiments,execution of one or more of the control protocols can be based on apredetermined time period. For example, execution of the first controlprotocol can be carried out for 50 seconds, followed by commencement ofthe second control protocol. For example, execution of the secondcontrol protocol can be carried out for 90 seconds, after which it isstopped; it may then optionally be re-executed based on sensing of oneor more physiological parameters.

In an embodiment, shown in FIG. 9, the control circuitry 708 of thesystem 700 further includes a third control protocol 900. The thirdcontrol protocol 900 can relate to determining whether and when toadminister iodide to the heart, such as by dictating whether and when togenerate one or more control signals that cause the metabolic moleculesupply device 706 to supply iodide (or one or more salts thereof) tocardiac tissue. Iodide provides benefits from reperfusion injurysuffered by heart tissue from acute myocardial infarction (see, e.g.,Iwata et al., incorporated by reference herein). For instance, hearttissue is temporarily deprived of oxygen during an acute myocardialinfarction, causing a decrease in oxygen consumption in an attempt toregulate oxygen levels. When blood flow is restored post reperfusion,oxygen consumption can increase to levels several fold higher thanbefore the ischemic event. This excessive oxygen consumption period cancause damage to heart tissue, such as inflammation and cell death.Iodide can perform a therapeutic role regarding cardiac tissue damageresulting from reperfusion. In embodiments, the control circuitry 708 isconfigured to execute the third control protocol 900 upon detection of afibrillation event to cause the control circuitry 708 to generate one ormore control signals that cause the metabolic molecule supply device 706to supply iodide to cardiac tissue. In embodiments, the controlcircuitry 708 is configured to execute the third control protocol 900prior to execution of the first control protocol 710 and the secondcontrol protocol 712. For example, since each of the first controlprotocol 710 and the second control protocol 712 are directed toproviding electric stimulation of cardiac tissue, which could result inreperfusion of blood to heart tissue, the supply of iodide to thecardiac tissue prior to reperfusion of blood can aid in protecting theheart tissue from ischemia reperfusion injury.

In embodiments, the system 700 is configured to supply one or morenon-oxygen cellular energy sources to one or more tissues of the heart.For example, in an embodiment, the metabolic molecule supply device 706is configured to supply one or more non-oxygen cellular energy sourcesto one or more tissues of the heart, such by introducing the one or morenon-oxygen cellular energy sources to an interface between a bloodstream and the metabolic molecule supply device 706. In embodiments, theone or more non-oxygen cellular energy sources can include, but are notlimited to adenosine triphosphate (ATP), cyclic adenosine monophosphate(cAMP), adenosine monophosphate (AMP), adenosine diphosphate (ADP),creatine, and cyclocreatine. In embodiments, the one or more non-oxygencellular energy sources are supplied as a result of execution by thecontrol circuitry 708 of one or more of the first control protocol 710,the second control protocol 712, the third control protocol 900, andanother control protocol.

The systems 100 and 700 can include one or more power sources configuredto provide power to one or more components of the systems. For example,in embodiments, as shown in FIG. 10, the system 700 includes a powersupply 1000 configured to provide power to one or more components of thesystem 700 including, but not limited to, the electromagnetic signalgenerator 704, the metabolic molecule supply device 706, and the controlcircuitry 708. In embodiments, the power supply 1000 is a residentdevice component that is coupled to the substrate 702. Examples ofresident device components include, but are not limited to, batteries(e.g., a thin film battery, a microbattery) and solar cells (e.g.,silicon-based solar cells) configured to convert light energy intoelectrical energy for use by the components of the systems describedherein. In embodiments, the power supply 1000 includes one or morecomponents positioned remotely from the substrate 702 that transmitpower signals via associated wireless power methods including, but notlimited to, inductive coupling of power signals. In such embodiments,the system 700 includes one or more components positioned on thesubstrate 702 configured to one or more of receive, process, and/ordistribute the power signals that originate from components positionedremotely from the substrate 702. For example, the system 700 can includea wireless power coil coupled to the substrate 702 that is configured toreceive a remote power signal, such as a remote power signal originatingfrom a remote transmission coil.

In an embodiment, shown in FIG. 11A, a system (or device) 1100 isconfigured to treat cardiac tissue, such as cardiac tissue during andfollowing a fibrillation event. The system 1100 includes, but is notlimited to, a substrate 1102, an electromagnetic signal generator 1104,and an energy-carrier molecule delivery device 1106. The substrate 1102is configured for implantation within a body of an individual and tohouse or support other portions of the system 1100. In embodiments, thestructure of the substrate 1102 is similar to, or the same as, thestructure of the substrates 102 and 702 described herein, withcorresponding functionalities. The electromagnetic signal generator 1104is coupled to the substrate 1102 and is configured to generate one ormore electric signals configured to stimulate one or more tissues of theheart within the individual's body. In embodiments, the structure of theelectromagnetic signal generator 1104 is similar to, or the same as, thestructure of the electromagnetic signal generators 104 and 704 describedherein, with corresponding functionalities.

The energy-carrier molecule delivery device 1106 is coupled to thesubstrate 1102 and is configured to supply one or more non-oxygencellular energy sources to one or more tissues of the heart within thebody. In embodiments, the one or more non-oxygen cellular energy sourcescan include, but are not limited to adenosine triphosphate (ATP), cyclicadenosine monophosphate (cAMP), adenosine monophosphate (AMP), adenosinediphosphate (ADP), creatine, and cyclocreatine. In embodiments, thenon-oxygen cellular energy sources include one or more carrier moleculesconfigured to transport the non-oxygen cellular energy source (e.g.,ATP). The carrier molecules can include, but are not limited to,liposomes, micelles, and perflurocarbons. In embodiments, the carriermolecules include a targeting agent configured to target cardiactissues, such as ischemic cardiac tissues. The targeting agent caninclude, but is not limited to an antibody, an aptamer, and the like,configured to bind to a distinct target protein. In embodiments, thecarrier molecules include an endocytosis-promoting agent. Theendocytosis-promoting agent can include, but is not limited to, aclathrin, a liposome, a transferrin, a growth factor, an antibody, anaptamer, and the like. In embodiments, the energy-carrier moleculedelivery device 1106 includes a reservoir (e.g., reservoir 1108) or isin fluid communication with a reservoir, or a combination of both, wherethe reservoir is configured to store the non-oxygen cellular energysources for use by the energy-carrier molecule delivery device 1106 tosupply the one or more non-oxygen cellular energy sources to the cardiactissue.

In an embodiment, shown in FIG. 11B, the energy-carrier moleculedelivery device 1106 includes a blood inlet portion 1110, an energymolecule exchange portion 1112, and a blood outlet portion 1114. Theblood inlet portion 1110 is configured to receive blood from theindividual in which the system 1100 is implanted into the energy-carriermolecule delivery device 1106 to provide a blood-energy-carrier moleculeexchange interface. The blood outlet portion 1114 is configured toreturn blood having the non-oxygen cellular energy sources to theindividual following blood-energy-carrier molecule exchange in theenergy molecule exchange portion 1112. The blood inlet portion 1110 andthe blood outlet portion 1114 can include various fluid-flow passagewaysand ports suitable for the transport of blood, and can include, but arenot limited to, biocompatible capillary conduits/tubes and micron-scaleconduits/tubes (e.g., sufficient to transport at least one red bloodcell through the interior of the tube or between the exterior ofneighboring tubes). In embodiments, at least a portion of the conduitsof the system 1100 have an internal diameter (or inter-conduitseparation) of greater than 10 microns to accommodate the passage of redblood cells. For example, in embodiments, at least a portion of theconduits of the system 100 have a minimum internal diameter of between10 microns and 12 microns to accommodate the passage of red blood cellsthrough the system 100. The internal diameter may be larger or smallerthan this range, due to manufacturing tolerances, design specificationsdependent on types of red blood cells, and so forth, to accommodate thepassage of red bloods cells, such as in a flow of singular red bloodscells. In embodiments, the energy molecule exchange portion 1112includes a high surface area exchanger 1116 configured to transfer theone or more metabolic molecules to blood in contact with the highsurface area exchanger 1116. In general, the high surface area exchanger1116 facilitates exchange between the blood and metabolic molecules byproviding a significant surface area for diffusion into and through theblood phase.

The source of the blood to be received by the blood inlet portion 1110and the destination of the blood to be returned by the blood outletportion 1114 may depend on design characteristics of the system 1100,including size of the substrate 1102, number of inlets of the bloodinlet portion 1110, number of outlets of the blood outlet portion 1114,portion of cardiac tissue to be treated, presence or absence of a bloodpump, and so forth. The source of the blood to be received by the bloodinlet portion 1110 and the destination of the oxygenated blood to bereturned by the blood outlet portion 1114 may include sources anddestinations employed for extracorporeal membrane oxygenators (see,e.g., Hung, et al., ibid., incorporated herein by reference).

For example, in an embodiment, the blood inlet portion 1110 includes oneor more ports configured to receive blood from one or more cardiacveins, such as from one or more of the great cardiac vein (e.g., leftcoronary vein), the middle cardiac vein, the small cardiac vein, and atleast one of the anterior cardiac veins (e.g., anterior veins of rightventricle); the blood is then oxygenated by the energy molecule exchangeportion 1112, and subsequently returned by the blood outlet portion 1114having at least one port positioned within at least one coronary artery,such as within a portion of one or more of the left coronary artery, theright coronary artery, and one or more subendocardial artery.

In an embodiment, the blood inlet portion 1110 includes one or moreports in contact with blood from an internal jugular vein, andconfigured to receive blood from one or more of the superior vena cava(SVC) and the inferior vena cava (IVC), where after introduction of thenon-oxygen cellular energy molecule to the blood occurs in the energymolecule exchange portion 1112, the blood is returned to the individualvia a port of the blood outlet portion 1114 positioned within at leastone coronary artery, such as within a portion of one or more of the leftcoronary artery, the right coronary artery, and one or moresubendocardial artery. The blood inlet portion 1110 can include at leasttwo ports, with at least one port positioned to receive blood from thesuperior vena cava (SVC) and at least one port positioned to receiveblood from the inferior vena cava (IVC).

In an embodiment, the blood inlet portion 1110 includes one or moreports in contact with blood from an internal jugular vein, andconfigured to receive blood from one or more of the superior vena cava(SVC) and the inferior vena cava (IVC), where after introduction of thenon-oxygen cellular energy molecule to the blood occurs in the energymolecule exchange portion 1112, the blood is returned to the individualvia a port of the blood outlet portion 1114 positioned within orproximate to the right atrium of the heart. The blood inlet portion 1110can include at least two ports, with at least one port positioned toreceive blood from the superior vena cava (SVC) and at least one portpositioned to receive blood from the inferior vena cava (IVC).

In an embodiment, the blood inlet portion 1110 includes a port incontact with blood from an internal jugular vein, and is configured toreceive blood from one or more of the superior vena cava (SVC) and theinferior vena cava (IVC), where after introduction of the non-oxygencellular energy molecule to the blood occurs in the energy moleculeexchange portion 1112, the blood is returned to the individual via aport of the blood outlet portion 1114 positioned within or proximate toone or more of the ascending aorta, the descending aorta, and the aorticarch.

In an embodiment, the blood inlet portion 1110 includes a port incontact with blood from at least one of the pulmonary artery and theright ventricle, where after oxygenation of the blood occurs in theenergy molecule exchange portion 1112, the oxygenated blood is returnedto the individual via a port of the blood outlet portion 1114 positionedwithin or proximate to one or more of the pulmonary vein, and the leftatrium. In an embodiment, the blood inlet portion 1110 includes a portin contact with blood from at least one of the ascending aorta, thedescending aorta, the aortic arch, and the left ventricle, where afteroxygenation of the blood occurs in the energy molecule exchange portion1112, the oxygenated blood is returned to the individual via a port ofthe blood outlet portion 1114 positioned within or proximate to one ormore of the superior vena cava, the inferior vena cava, and the rightatrium. In an embodiment, the blood inlet portion 1110 includes a portin contact with blood from at least one of the ascending aorta, thedescending aorta, the aortic arch, and the left ventricle, where afteroxygenation of the blood occurs in the energy molecule exchange portion1112, the oxygenated blood is returned to the individual via a port ofthe blood outlet portion 1114 positioned within or proximate to one ormore of the pulmonary vein, and the left atrium. In an embodiment, theblood inlet portion 1110 includes a port in contact with blood from atleast one of the descending aorta, the mesenteric artery, the iliacartery, and the femoral artery, where after oxygenation of the bloodoccurs in the energy molecule exchange portion 1112, the oxygenatedblood is returned to the individual via a port of the blood outletportion 1114 positioned within or proximate to one or more of thefemoral vein, the iliac vein, the abdominal vena cava, the inferior venacava, and the right atrium. Other configurations are possible and arenot limited to the above-provided configurations.

In some embodiments, the energy-carrier molecule delivery device 1106includes a blood pump 1118. The blood pump 1118 may be coupled to theblood inlet portion 1110, and may be used to force blood through theenergy molecule exchange portion 1112 (e.g., overcoming the flowresistance through high surface area exchanger 1116). In someembodiments, the blood pump 1118 may be controlled so as to match thepressure at the blood outlet portion 1114 to that of the blood in thedestination lumen. Blood pump 1118 may include the same type of bloodpumps (e.g., centrifugal types, or roller types) typically used inconjunction with extracorporeal membrane oxygenators. Unlike pumps usedin implantable “artificial hearts,” the blood pump 1118 can beconfigured to operate only for short durations, i.e., during afibrillation event. The blood pump 1118 may facilitate operation ofembodiments where the blood inlet portion 1110 is coupled to a vein or aheart atrium, and may be optional in some embodiments (e.g., embodimentswhere the blood inlet portion 1110 is coupled to an artery or heartventricle).

In some embodiments, the energy-carrier molecule delivery portion 1106includes a controllable valve 1120. The valve 1120 may be coupled to theblood inlet portion 1110, and may be closed during normal situations toprevent blood flow through the energy-carrier molecule delivery portion1106 (e.g., through energy molecule exchange portion 1112), and openedonly during fibrillation events.

In an embodiment, shown in FIG. 12, the system 1100 includes controlcircuitry 1200 configured to generate one or more control signals basedupon execution of one or more control protocols, such as a first controlprotocol 1202 and a second control protocol 1204. In embodiments, uponexecution by the control circuitry 1200 of the first control protocol1202, the control circuitry 1200 generates one or more control signalsthat cause the electromagnetic signal generator 1104 to generate one ormore electric signals configured to stimulate cardiac tissues. Forexample, the first control protocol 1202 can provide direction regardingactions for the system 1100 to take during a fibrillation event. Inembodiments, upon execution by the control circuitry 1200 of the secondcontrol protocol 1204, the control circuitry 1200 generates one or morecontrol signals that cause the electromagnetic signal generator 1104 togenerate one or more electric signals configured to stimulate cardiactissues and the control circuitry 1200 generates one or more controlsignals that cause the energy-carrier molecule delivery device 1106 tosupply the one or more non-oxygen cellular energy sources to one or morecardiac tissues. For example, the second control protocol 1204 canprovide direction regarding actions for the system 1100 to take duringan extended fibrillation event where non-oxygen cellular energy sources,such as ATP are beneficial in attempting to treat a heart undergoingsystemic shock associated with exhaustion of myoglobin-based oxygenstorage (e.g., a period of fifty seconds to seventy-five secondsfollowing onset of a fibrillation event). In embodiments, the controlcircuitry 1200 determines which control protocol to execute based onmeasurements from one or more physiological sensors. The one or morephysiological sensors can be included as a component of the system 1100,located remotely from the system 1100, or a combination of resident andremote sensors. In embodiments, the physiological sensor is a bloodpressure sensor configured to measure a blood pressure of an aorticregion, a coronary artery, a cardiac vein, and the like, to determinewhether the heart is undergoing a fibrillation event. For example, thephysiological sensor can measure the blood pressure at the aortic archto determine whether the heart is undergoing a fibrillation event. Inembodiments, the physiological sensor includes an oxygenation sensorconfigured to measure a cardiac oxygenation level, such as anoxygenation level of cardiac tissue-based myoglobin. When a fibrillationevent is detected by the physiological sensor, the physiological sensor(or associated control circuitry) can provide an indication (e.g., inthe form of sense signals, control signals, and so forth) to the controlcircuitry 1200 regarding the fibrillation event. This indication caninclude, but is not limited to, whether a fibrillation event isoccurring, the current duration of the fibrillation event, and the like.The control circuitry 1200 can then provide control signals to one ormore of the electromagnetic signal generator 1104 and the energy-carriermolecule delivery device 1106 for treatment of the cardiac tissue duringthe fibrillation event. In embodiments, the control circuitry 1200provides control signals to the electromagnetic signal generator 1104,independent of the energy-carrier molecule delivery device 1106, such asprovided by the first control protocol 1202. In embodiments, the controlcircuitry 1200 provides control signals to each of the electromagneticsignal generator 1104 and the energy-carrier molecule delivery device1106, such as provided by the second control protocol 1204.

In embodiments, the control circuitry 1200 generates the control signalsbased on commands issued by an external control device (shown as 1300 inFIG. 13). In embodiments, the control circuitry 1200 can send andreceive signals between external control device 1300 via associatedwireless communication methods including, but not limited to acousticcommunication signals, optical communication signals, radiocommunication signals, infrared communication signals, ultrasoniccommunication signals, and the like. The control circuitry 1200 caninclude a microprocessor, a central processing unit (CPU), a digitalsignal processor (DSP), an application-specific integrated circuit(ASIC), a field programmable gate entry (FPGA), or the like, or anycombinations thereof, and can include discrete digital or analog circuitelements or electronics, or combinations thereof. In one embodiment, thecomputing device includes one or more ASICs having a plurality ofpredefined logic components. In one embodiment, the computing deviceincludes one or more FPGAs having a plurality of programmable logiccommands.

In embodiments, the control circuitry 1200 is configured to receive oneor more control signals from the external control device 1300 and tomake a determination regarding a defibrillation state. For example, thecontrol circuitry 1200 can receive one or more control signals from theexternal control device 1300, whereby the control circuitry 1200 directsone or more physiological sensors to measure a physiological parameterassociated with cardiac activity (e.g., blood pressure, bloodoxygenation level, myoglobin oxygenation level, and the like) todetermine a defibrillation state of the individual in which the system1100 is implanted. Based upon the physiological parameter of the heart,the control circuitry 1200 can execute the first control protocol 1202or the second control protocol 1204. For example, in embodiments, whenthe physiological parameter of the heart indicates a fibrillation eventis occurring, and the myoglobin-based oxygen is not exhausted (e.g., aperiod between onset of a fibrillation event and between approximatelyfifty seconds and seventy-five seconds following the onset of thefibrillation event), the control circuitry 1200 executes the firstcontrol protocol 1202, resulting in activation of the electromagneticsignal generator 1104 for electric stimulation of the cardiac tissue. Inembodiments, when the physiological parameter of the heart indicates afibrillation event is occurring, and the myoglobin-based oxygen issubstantially exhausted (e.g., a period of fifty seconds to seventy-fiveseconds following onset of a fibrillation event, exhaustion of greaterthan 50%, etc.), the control circuitry 1200 executes the second controlprotocol 1204, resulting in activation of each of the electromagneticsignal generator 1104 and the energy-carrier molecule delivery device1106 for treatment of the cardiac tissue, such as through electricstimulation of the cardiac tissue and delivery of non-oxygen cellularenergy sources to the cardiac tissue.

In embodiments, the system 1100 is configured to supply one or morematerials to the blood in addition to the non-oxygen cellular energysources. For example, the materials in addition to the non-oxygencellular energy sources can include, but are not limited to, hydrogensulfide (H₂S), carbon dioxide (CO₂), carbon monoxide (CO), nitric oxide(NO), nitrous oxide (N₂O), and nitrogen dioxide (NO₂), and iodide (e.g.,iodide ions (I⁻) and salts thereof (e.g., sodium iodide (NaI)), see,e.g., Iwata et al., incorporated herein by reference). These materialscan be used to protect the cardiac tissue from injury (e.g., ischemiareperfusion injury) during and after a fibrillation event, to controlmetabolic processes of cardiac tissue during and after a fibrillationevent, to provide localized or systemic anesthetic, and so forth.

FIG. 14 illustrates a method 1400 for treating a heart with an implantedheart treatment device in accordance with example embodiments. Method1400 shows generating, via a heart treatment device implanted within abody of a biological subject, one or more electric signals configured tostimulate one or more tissues of a heart within a body during afibrillation event of the heart in block 1402. For example, theelectromagnetic generator 104 of system 100 can generate one or moreelectric signals configured to stimulate one or more tissues of a heartwithin a body during a fibrillation event of the heart, such asresponsive to control by control circuitry 600. Method 1400 alsoincludes administering the one or more electric signals to the one ormore tissues of the heart in block 1404. For example, theelectromagnetic generator 104 of system 100 can administer the one ormore electric signals to the one or more tissues of the heart, such asresponsive to control by control circuitry 600. Method 1400 alsoincludes delivering, via the heart treatment device, one or moreoxygenated molecules to one or more tissues of the heart, after thefibrillation event has proceeded for a duration sufficient to at leastsubstantially exhaust the myoglobin-based oxygen of the heart in block1406. For example, the oxygenator 106 can deliver one or more oxygenatedmolecules to blood via the oxygen exchange portion 202, whenphysiological sensors provide an indication of an occurrence andduration of a fibrillation event of the heart.

FIG. 15 illustrates a method 1500 for treating a heart with an implantedheart treatment device in accordance with example embodiments. Method1500 shows generating, via a heart treatment device implanted within abody of a biological subject, one or more electric signals configured tostimulate one or more tissues of a heart within a body during afibrillation event of the heart according to a first control protocoland a second control protocol in block 1502. For example, theelectromagnetic generator 704 of system 700 can generate one or moreelectric signals configured to stimulate one or more tissues of a heartwithin a body during a fibrillation event of the heart, responsive tocontrol by control circuitry 708 upon execution of the first controlprotocol 710 and the second control protocol 712. Method 1500 alsoincludes administering the one or more electric signals to the one ormore tissues of the heart according to the first control protocol andthe second control protocol in block 1504. For example, theelectromagnetic generator 704 of system 700 can administer the one ormore electric signals to the one or more tissues of the heart,responsive to control by control circuitry 708 upon execution of thefirst control protocol 710 and the second control protocol 712. Method1500 also includes delivering, via the heart treatment device, one ormore metabolic molecules to one or more tissues of the heart, after thefibrillation event has proceeded for a duration sufficient to at leastsubstantially exhaust the myoglobin-based oxygen of the heart accordingto the second control protocol in block 1506. For example, the metabolicmolecule delivery device 706 can deliver one or more metabolic moleculesto blood, responsive to control by control circuitry 708 upon executionof the second control protocol 712.

FIG. 16 illustrates a method 1600 for treating a heart with an implantedheart treatment device in accordance with example embodiments. Method1600 shows generating, via a heart treatment device implanted within abody of a biological subject, one or more electric signals configured tostimulate one or more tissues of a heart within a body during afibrillation event of the heart in block 1602. For example, theelectromagnetic generator 1104 of system 1100 can generate one or moreelectric signals configured to stimulate one or more tissues of a heartwithin a body during a fibrillation event of the heart, such asresponsive to control by control circuitry 1200. Method 1600 alsoincludes administering the one or more electric signals to the one ormore tissues of the heart in block 1604. For example, theelectromagnetic generator 1104 of system 1100 can administer the one ormore electric signals to the one or more tissues of the heart, such asresponsive to control by control circuitry 1200. Method 1600 alsoincludes delivering, via the heart treatment device, one or morenon-oxygen cellular energy sources to one or more tissues of the heart,after the fibrillation event has proceeded for a duration sufficient toat least substantially exhaust the myoglobin-based oxygen of the heartin block 1606. For example, the energy-carrier molecule delivery portion1106 can deliver one or more non-oxygen cellular energy sources to bloodvia the energy molecule exchange portion 1112, when physiologicalsensors provide an indication of an occurrence and duration of afibrillation event of the heart.

The state of the art has progressed to the point where there is littledistinction left between hardware, software, and/or firmwareimplementations of aspects of systems; the use of hardware, software,and/or firmware is generally (but not always, in that in certaincontexts the choice between hardware and software can becomesignificant) a design choice representing cost vs. efficiency tradeoffs.There are various vehicles by which processes and/or systems and/orother technologies described herein can be effected (e.g., hardware,software, and/or firmware), and that the preferred vehicle will varywith the context in which the processes and/or systems and/or othertechnologies are deployed. For example, if an implementer determinesthat speed and accuracy are paramount, the implementer may opt for amainly hardware and/or firmware vehicle; alternatively, if flexibilityis paramount, the implementer may opt for a mainly softwareimplementation; or, yet again alternatively, the implementer may opt forsome combination of hardware, software, and/or firmware. Hence, thereare several possible vehicles by which the processes and/or devicesand/or other technologies described herein can be effected, none ofwhich is inherently superior to the other in that any vehicle to beutilized is a choice dependent upon the context in which the vehiclewill be deployed and the specific concerns (e.g., speed, flexibility, orpredictability) of the implementer, any of which may vary. Those skilledin the art will recognize that optical aspects of implementations willtypically employ optically-oriented hardware, software, and or firmware.

In some implementations described herein, logic and similarimplementations can include software or other control structures.Electronic circuitry, for example, may have one or more paths ofelectrical current constructed and arranged to implement variousfunctions as described herein. In some implementations, one or moremedia can be configured to bear a device-detectable implementation whensuch media hold or transmit a device detectable instructions operable toperform as described herein. In some variants, for example,implementations can include an update or modification of existingsoftware or firmware, or of gate arrays or programmable hardware, suchas by performing a reception of or a transmission of one or moreinstructions in relation to one or more operations described herein.Alternatively or additionally, in some variants, an implementation caninclude special-purpose hardware, software, firmware components, and/orgeneral-purpose components executing or otherwise invokingspecial-purpose components. Specifications or other implementations canbe transmitted by one or more instances of tangible transmission mediaas described herein, optionally by packet transmission or otherwise bypassing through distributed media at various times.

Alternatively or additionally, implementations may include executing aspecial-purpose instruction sequence or otherwise invoking circuitry forenabling, triggering, coordinating, requesting, or otherwise causing oneor more occurrences of any functional operations described above. Insome variants, operational or other logical descriptions herein may beexpressed directly as source code and compiled or otherwise invoked asan executable instruction sequence. In some contexts, for example, C++or other code sequences can be compiled directly or otherwiseimplemented in high-level descriptor languages (e.g., alogic-synthesizable language, a hardware description language, ahardware design simulation, and/or other such similar mode(s) ofexpression). Alternatively or additionally, some or all of the logicalexpression may be manifested as a Verilog-type hardware description orother circuitry model before physical implementation in hardware,especially for basic operations or timing-critical applications.

The foregoing detailed description has set forth various embodiments ofthe devices and/or processes via the use of block diagrams, flowcharts,and/or examples. Insofar as such block diagrams, flowcharts, and/orexamples contain one or more functions and/or operations, each functionand/or operation within such block diagrams, flowcharts, or examples canbe implemented, individually and/or collectively, by a wide range ofhardware, software, firmware, or virtually any combination thereof. Inone embodiment, several portions of the subject matter described hereincan be implemented via Application Specific Integrated Circuits (ASICs),Field Programmable Gate Arrays (FPGAs), digital signal processors(DSPs), or other integrated formats. However, some aspects of theembodiments disclosed herein, in whole or in part, can be equivalentlyimplemented in integrated circuits, as one or more computer programsrunning on one or more computers (e.g., as one or more programs runningon one or more computer systems), as one or more programs running on oneor more processors (e.g., as one or more programs running on one or moremicroprocessors), as firmware, or as virtually any combination thereof,and that designing the circuitry and/or writing the code for thesoftware and or firmware would be well within the skill of one of skillin the art in light of this disclosure. In addition, the mechanisms ofthe subject matter described herein are capable of being distributed asa program product in a variety of forms, and that an illustrativeembodiment of the subject matter described herein applies regardless ofthe particular type of signal bearing medium used to actually carry outthe distribution.

In a general sense, the various embodiments described herein can beimplemented, individually and/or collectively, by various types ofelectro-mechanical systems having a wide range of electrical componentssuch as hardware, software, firmware, and/or virtually any combinationthereof and a wide range of components that may impart mechanical forceor motion such as rigid bodies, spring or torsional bodies, hydraulics,electro-magnetically actuated devices, and/or virtually any combinationthereof. Consequently, as used herein “electro-mechanical system”includes, but is not limited to, electrical circuitry operably coupledwith a transducer (e.g., an actuator, a motor, a piezoelectric crystal,a Micro Electro Mechanical System (MEMS), etc.), electrical circuitryhaving at least one discrete electrical circuit, electrical circuitryhaving at least one integrated circuit, electrical circuitry having atleast one application specific integrated circuit, electrical circuitryforming a general purpose computing device configured by a computerprogram (e.g., a general purpose computer configured by a computerprogram which at least partially carries out processes and/or devicesdescribed herein, or a microprocessor configured by a computer programwhich at least partially carries out processes and/or devices describedherein), electrical circuitry forming a memory device (e.g., forms ofmemory (e.g., random access, flash, read only, etc.)), electricalcircuitry forming a communications device (e.g., a modem, communicationsswitch, optical-electrical equipment, etc.), and/or any non-electricalanalog thereto, such as optical or other analogs. Examples ofelectro-mechanical systems include but are not limited to a variety ofconsumer electronics systems, medical devices, as well as other systemssuch as motorized transport systems, factory automation systems,security systems, and/or communication/computing systems.Electro-mechanical as used herein is not necessarily limited to a systemthat has both electrical and mechanical actuation except as context maydictate otherwise.

In a general sense, the various aspects described herein can beimplemented, individually and/or collectively, by a wide range ofhardware, software, firmware, and/or any combination thereof and can beviewed as being composed of various types of “electrical circuitry.”Consequently, as used herein “electrical circuitry” includes, but is notlimited to, electrical circuitry having at least one discrete electricalcircuit, electrical circuitry having at least one integrated circuit,electrical circuitry having at least one application specific integratedcircuit, electrical circuitry forming a general purpose computing deviceconfigured by a computer program (e.g., a general purpose computerconfigured by a computer program which at least partially carries outprocesses and/or devices described herein, or a microprocessorconfigured by a computer program which at least partially carries outprocesses and/or devices described herein), electrical circuitry forminga memory device (e.g., forms of memory (e.g., random access, flash, readonly, etc.)), and/or electrical circuitry forming a communicationsdevice (e.g., a modem, communications switch, optical-electricalequipment, etc.). The subject matter described herein can be implementedin an analog or digital fashion or some combination thereof.

At least a portion of the systems and/or processes described herein canbe integrated into an image processing system. A typical imageprocessing system generally includes one or more of a system unithousing, a video display device, memory such as volatile or non-volatilememory, processors such as microprocessors or digital signal processors,computational entities such as operating systems, drivers, applicationsprograms, one or more interaction devices (e.g., a touch pad, a touchscreen, an antenna, etc.), control systems including feedback loops andcontrol motors (e.g., feedback for sensing lens position and/orvelocity; control motors for moving/distorting lenses to give desiredfocuses). An image processing system can be implemented utilizingsuitable commercially available components, such as those typicallyfound in digital still systems and/or digital motion systems.

At least a portion of the systems and/or processes described herein canbe integrated into a data processing system. A data processing systemgenerally includes one or more of a system unit housing, a video displaydevice, memory such as volatile or non-volatile memory, processors suchas microprocessors or digital signal processors, computational entitiessuch as operating systems, drivers, graphical user interfaces, andapplications programs, one or more interaction devices (e.g., a touchpad, a touch screen, an antenna, etc.), and/or control systems includingfeedback loops and control motors (e.g., feedback for sensing positionand/or velocity; control motors for moving and/or adjusting componentsand/or quantities). A data processing system can be implementedutilizing suitable commercially available components, such as thosetypically found in data computing/communication and/or networkcomputing/communication systems.

At least a portion of the systems and/or processes described herein canbe integrated into a mote system. Those having skill in the art willrecognize that a typical mote system generally includes one or morememories such as volatile or non-volatile memories, processors such asmicroprocessors or digital signal processors, computational entitiessuch as operating systems, user interfaces, drivers, sensors, actuators,applications programs, one or more interaction devices (e.g., an antennaUSB ports, acoustic ports, etc.), control systems including feedbackloops and control motors (e.g., feedback for sensing or estimatingposition and/or velocity; control motors for moving and/or adjustingcomponents and/or quantities). A mote system may be implementedutilizing suitable components, such as those found in motecomputing/communication systems. Specific examples of such componentsentail such as Intel Corporation's and/or Crossbow Corporation's motecomponents and supporting hardware, software, and/or firmware.

The herein described components (e.g., operations), devices, objects,and the discussion accompanying them are used as examples for the sakeof conceptual clarity and that various configuration modifications arecontemplated. Consequently, as used herein, the specific exemplars setforth and the accompanying discussion are intended to be representativeof their more general classes. In general, use of any specific exemplaris intended to be representative of its class, and the non-inclusion ofspecific components (e.g., operations), devices, and objects should notbe taken limiting.

With respect to the use of substantially any plural and/or singularterms herein, the plural can be translated to the singular and/or fromthe singular to the plural as is appropriate to the context and/orapplication. The various singular/plural permutations are not expresslyset forth herein for sake of clarity.

The herein described subject matter sometimes illustrates differentcomponents contained within, or connected with, different othercomponents. It is to be understood that such depicted architectures aremerely exemplary, and that in fact many other architectures can beimplemented which achieve the same functionality. In a conceptual sense,any arrangement of components to achieve the same functionality iseffectively “associated” such that the desired functionality isachieved. Hence, any two components herein combined to achieve aparticular functionality can be seen as “operably coupled to” each othersuch that the desired functionality is achieved, irrespective ofarchitectures or intermedial components. Likewise, any two components soassociated can also be viewed as being “operably connected,” or“operably coupled,” to each other to achieve the desired functionality,and any two components capable of being so associated can also be viewedas being “operably couplable,” to each other to achieve the desiredfunctionality. Specific examples of operably couplable include but arenot limited to physically mateable and/or physically interactingcomponents, and/or wirelessly interactable, and/or wirelesslyinteracting components, and/or logically interacting, and/or logicallyinteractable components.

In some instances, one or more components can be referred to herein as“configured to,” “configured by,” “configurable to,” “operable/operativeto,” “adapted/adaptable,” “able to,” “conformable/conformed to,” etc.Those skilled in the art will recognize that such terms (e.g.“configured to”) can generally encompass active-state components and/orinactive-state components and/or standby-state components, unlesscontext requires otherwise.

While particular aspects of the present subject matter described hereinhave been shown and described, based upon the teachings herein, changesand modifications can be made without departing from the subject matterdescribed herein and its broader aspects and, therefore, the appendedclaims are to encompass within their scope all such changes andmodifications as are within the true spirit and scope of the subjectmatter described herein.

In general, terms used herein, and especially in the appended claims(e.g., bodies of the appended claims) are generally intended as “open”terms (e.g., the term “including” should be interpreted as “includingbut not limited to,” the term “having” should be interpreted as “havingat least,” the term “includes” should be interpreted as “includes but isnot limited to,” etc.). If a specific number of an introduced claimrecitation is intended, such an intent will be explicitly recited in theclaim, and in the absence of such recitation no such intent is present.For example, as an aid to understanding, the following appended claimsmay contain usage of the introductory phrases “at least one” and “one ormore” to introduce claim recitations. However, the use of such phrasesshould not be construed to imply that the introduction of a claimrecitation by the indefinite articles “a” or “an” limits any particularclaim containing such introduced claim recitation to claims containingonly one such recitation, even when the same claim includes theintroductory phrases “one or more” or “at least one” and indefinitearticles such as “a” or “an” (e.g., “a” and/or “an” should typically beinterpreted to mean “at least one” or “one or more”); the same holdstrue for the use of definite articles used to introduce claimrecitations. In addition, even if a specific number of an introducedclaim recitation is explicitly recited, those skilled in the art willrecognize that such recitation should typically be interpreted to meanat least the recited number (e.g., the bare recitation of “tworecitations,” without other modifiers, typically means at least tworecitations, or two or more recitations). Furthermore, in thoseinstances where a convention analogous to “at least one of A, B, and C,etc.” is used, in general such a construction is intended in the senseone having skill in the art would understand the convention (e.g., “asystem having at least one of A, B, and C” would include but not belimited to systems that have A alone, B alone, C alone, A and Btogether, A and C together, B and C together, and/or A, B, and Ctogether, etc.). In those instances where a convention analogous to “atleast one of A, B, or C, etc.” is used, in general such a constructionis intended in the sense one having skill in the art would understandthe convention (e.g., “a system having at least one of A, B, or C” wouldinclude but not be limited to systems that have A alone, B alone, Calone, A and B together, A and C together, B and C together, and/or A,B, and C together, etc.). Typically a disjunctive word and/or phrasepresenting two or more alternative terms, whether in the description,claims, or drawings, should be understood to contemplate thepossibilities of including one of the terms, either of the terms, orboth terms unless context dictates otherwise. For example, the phrase “Aor B” will be typically understood to include the possibilities of “A”or “B” or “A and B.”

While various aspects and embodiments have been disclosed herein, otheraspects and embodiments will be apparent to those skilled in the art.The various aspects and embodiments disclosed herein are for purposes ofillustration and are not intended to be limiting, with the true scopeand spirit being indicated by the following claims.

1. An implantable heart treatment device, comprising: a substrate configured for implantation within a body; an electromagnetic signal generator coupled to the substrate and configured to generate one or more electric signals configured to stimulate one or more tissues of a heart within the body; and an energy-carrier molecule delivery device coupled to the substrate and configured to supply one or more non-oxygen cellular energy sources to one or more tissues of the heart within the body.
 2. The implantable heart treatment device of claim 1, wherein the one or more non-oxygen cellular energy sources include at least one of adenosine triphosphate (ATP), cyclic adenosine monophosphate (cAMP), adenosine monophosphate (AMP), adenosine diphosphate (ADP), creatine, and cyclocreatine. 3.-6. (canceled)
 7. The implantable heart treatment device of claim 1, wherein the energy-carrier molecule delivery device includes a reservoir configured to store the one or more non-oxygen cellular energy sources molecules.
 8. The implantable heart treatment device of claim 1, wherein the one or more non-oxygen cellular energy sources are positioned within one or more carrier molecules. 9.-11. (canceled)
 12. The implantable heart treatment device of claim 8, wherein the one or more carrier molecules include at least one targeting agent configured to target cardiac tissue.
 13. (canceled)
 14. The implantable heart treatment device of claim 12, wherein the targeting agent includes at least one of an antibody configured to bind to a distinct target protein and an aptamer configured to bind to a distinct target protein.
 15. The implantable heart treatment device of claim 8, wherein the one or more carrier molecules include at least one endocytosis-promoting agent.
 16. The implantable heart treatment device of claim 15, wherein the endocytosis-promoting agent includes at least one of a clathrin, a liposome, a transferrin, a growth factor, an antibody, and an aptamer.
 17. The implantable heart treatment device of claim 1, wherein the energy-carrier molecule delivery device includes a blood inlet portion, a blood outlet portion, and an energy molecule exchange portion positioned between the blood inlet portion and the blood outlet portion.
 18. The implantable heart treatment device of claim 17, wherein at least one of the blood inlet portion and the blood outlet portion includes at least one conduit having an internal diameter greater than ten microns. 19.-23. (canceled)
 24. The implantable heart treatment device of claim 1, further comprising: control circuitry configured to generate one or more controls signals to activate one or more of the electromagnetic signal generator and the energy-carrier molecule delivery device.
 25. The implantable heart treatment device of claim 24, wherein the control circuitry is configured to wirelessly transmit information associated with the one or more control signals to an external device.
 26. The implantable heart treatment device of claim 24, wherein the control circuitry is configured to generate the one or more controls signals to activate one or more of the electromagnetic signal generator and the energy-carrier molecule delivery device during a fibrillation event of the heart.
 27. (canceled)
 28. (canceled)
 29. The implantable heart treatment device of claim 24, wherein the control circuitry is configured to receive one or more sense signals from one or more physiological sensors configured to measure one or more physiological parameters representative of the condition of the heart.
 30. The implantable heart treatment device of claim 29, wherein the control circuitry is configured to make a determination pertaining to a fibrillation event of the heart based on the one or more sense signals received from the one or more physiological sensors.
 31. The implantable heart treatment device of claim 30, wherein the control circuitry is configured to activate one or more of the electromagnetic signal generator and the energy-carrier molecule delivery device based on the determination pertaining to the fibrillation event of the heart.
 32. (canceled)
 33. (canceled)
 34. The implantable heart treatment device of claim 24, wherein the control circuitry is configured to generate the one or more controls signals to activate one or more of the electromagnetic signal generator and the energy-carrier molecule delivery device responsive to one or more commands from an external device.
 35. (canceled)
 36. The implantable heart treatment device of claim 24, wherein the control circuitry is configured to generate the one or more controls signals to activate the electromagnetic signal generator responsive to execution of a first control protocol.
 37. (canceled)
 38. (canceled)
 39. The implantable heart treatment device of claim 24, wherein the control circuitry is configured to generate the one or more controls signals to activate each of the electromagnetic signal generator and the energy-carrier molecule delivery device responsive to execution of a second control protocol.
 40. (canceled)
 41. (canceled)
 42. The implantable heart treatment device of claim 1, wherein the energy-carrier molecule delivery device is configured to supply one or more materials in addition to the one or more non-oxygen cellular energy sources.
 43. The implantable heart treatment device of claim 42, wherein the one or more materials in addition to the one or more non-oxygen cellular energy sources include at least one of hydrogen sulfide, carbon dioxide, carbon monoxide, nitric oxide, nitrous oxide, nitrogen dioxide, and iodide and salts thereof.
 44. A method of treating a heart with an implanted heart treatment device, comprising: generating, via a heart treatment device implanted within a body of a biological subject, one or more electric signals configured to stimulate one or more tissues of a heart within a body during a fibrillation event of the heart; administering the one or more electric signals to the one or more tissues of the heart; and delivering, via the heart treatment device, one or more non-oxygen cellular energy sources to one or more tissues of the heart, after the fibrillation event has proceeded for a duration sufficient to exhaust the myoglobin-based oxygen of the heart.
 45. The method of claim 44, wherein the one or more non-oxygen cellular energy sources include at least one of adenosine triphosphate (ATP), cyclic adenosine monophosphate (cAMP), adenosine monophosphate (AMP), adenosine diphosphate (ADP), creatine, and cyclocreatine. 46.-48. (canceled)
 49. The method of claim 44, further comprising: storing the one or more non-oxygen cellular energy sources molecules in vivo.
 50. The method of claim 44, further comprising: storing the one or more non-oxygen cellular energy sources in a reservoir of the heart treatment device.
 51. The method of claim 44, wherein the one or more more non-oxygen cellular energy sources are positioned within one or more carrier molecules. 52.-54. (canceled)
 55. The method of claim 51, wherein the one or more carrier molecules include at least one targeting agent configured to target cardiac tissue.
 56. (canceled)
 57. The method of claim 55, wherein the targeting agent includes at least one of an antibody configured to bind to a distinct target protein and an aptamer configured to bind to a distinct target protein.
 58. The method of claim 51, wherein the one or more carrier molecules include at least one endocytosis-promoting agent.
 59. The method of claim 58, wherein the endocytosis-promoting agent includes at least one of a clathrin, a liposome, a transferrin, a growth factor, an antibody, and an aptamer. 60.-64. (canceled)
 65. The method of claim 44, further comprising: determining a fibrillation state of the heart based on one or more sense signals corresponding to one or more physiological parameters representative of the condition of the heart.
 66. The method of claim 65, wherein administering the one or more electric signals to the one or more tissues of the heart includes: administering the one or more electric signals to the one or more tissues of the heart responsive to the determined fibrillation state.
 67. The method of claim 44, further comprising: determining a duration of a fibrillation state of the heart based on one or more sense signals corresponding to one or more physiological parameters representative of the condition of the heart.
 68. (canceled)
 69. (canceled)
 70. The method of claim 44, further comprising: wirelessly transmitting information associated with operation of the heart treatment device to an ex vivo device. 71.-74. (canceled)
 75. The method of claim 44, further comprising: administering one or more materials in addition to the one or more non-oxygen cellular energy sources.
 76. The method of claim 75, wherein the one or more materials in addition to the one or more non-oxygen cellular energy sources include at least one of hydrogen sulfide, carbon dioxide, carbon monoxide, nitric oxide, nitrous oxide, nitrogen dioxide, and iodide and salts thereof.
 77. The implantable heart treatment device of claim 8, wherein the one or more carrier molecules include at least one of one or more liposomes, one or more micelles, or one or more perflurocarbons.
 78. The implantable heart treatment device of claim 17, wherein the blood inlet portion includes one or more ports configured to at least one of receive blood from at least one vein of the body, receive blood from at least one artery of the body, return blood from the energy molecule exchange portion to a position directly within the heart, return blood from energy molecule exchange portion to at least one artery of the body, or return blood from the energy molecule exchange portion to at least one vein of the body.
 79. The implantable heart treatment device of claim 36, wherein the control circuitry is configured to execute the first control protocol during at least one of a fibrillation event of the heart and prior to exhaustion of myoglobin-based oxygen storage of the heart or a period from onset of a fibrillation event of the heart until between approximately fifty seconds and seventy-five seconds following onset of the fibrillation event.
 80. The implantable heart treatment device of claim 39, wherein the control circuitry is configured to execute the second control protocol during at least one of a fibrillation event of the heart after the fibrillation event has proceeded for a duration sufficient to exhaust the myoglobin-based oxygen of the heart or a fibrillation event of the heart during a period following between approximately fifty seconds and seventy-five seconds from onset of the fibrillation event.
 81. The method of claim 51, wherein the one or more carrier molecules include at least one of one or more liposomes, one or more micelles, or one or more perflurocarbons.
 82. The method of claim 44, wherein delivering, via the heart treatment device, one or more non-oxygen cellular energy sources to one or more tissues of the heart includes: receiving blood from at least one of a vein of the body or an artery of the body; and introducing the one or more non-oxygen cellular energy sources to the blood.
 83. The method of claim 44, wherein delivering, via the heart treatment device, one or more non-oxygen cellular energy sources to one or more tissues of the heart includes: receiving blood from a portion of the body; introducing the one or more non-oxygen cellular energy sources to the blood; and returning the blood to at least one of a position directly within the heart, an artery of the body, or a vein of the body.
 84. The method of claim 44, wherein generating, via a heart treatment device implanted within a body of a biological subject, one or more electric signals configured to stimulate one or more tissues of a heart within a body during a fibrillation event of the heart includes: generating, via a heart treatment device implanted within a body of a biological subject, one or more electric signals configured to stimulate one or more tissues of a heart within a body responsive to at least one of one or more sense signals generated by one or more physiological sensors or one or more control signals generated by an ex vivo control device.
 85. The method of claim 44, wherein administering the one or more electric signals to the one or more tissues of the heart includes: administering the one or more electric signals to the one or more tissues of the heart responsive to at least one of one or more sense signals generated by one or more physiological sensors or one or more control signals generated by an ex vivo control device.
 86. The method of claim 44, wherein delivering, via the heart treatment device, one or more non-oxygen cellular energy sources to one or more tissues of the heart, after the fibrillation event has proceeded for a duration sufficient to exhaust the myoglobin-based oxygen of the heart includes: delivering, via the heart treatment device, one or more non-oxygen cellular energy sources to one or more tissues of the heart, responsive to at least one of one or more sense signals generated by one or more physiological sensors or one or more control signals generated by an ex vivo control device. 